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The viruses are one of the most threatening factors for plants resulting in gigantic economic losses. These utilize host internal machinery for reproduction and can spread through biological and non-biological means. Among the most hazardous plant viruses, Tobacco mosaic virus (TMV) is the most ancient virus which causes massive economic losses to tobacco, pepper, cucumber and ornamental crops globally. The problem can be reduced by minimizing the vector population through application of pesticides. Opposite to obtained success in virus control, rapid utilization of synthetic chemicals is disastrous for our ecosystem. Therefore, alternative approaches such as natural derivatives should be explored for eco-friendly management of TMV. So, here we have tried to take into account various natural metabolites which can be effectively and potentially used against TMV. We further explained about the derivatives from animals, fungi, bacteria and actinomycetes which are useful against TMV. The review imbibes the recent research findings regarding exploration of natural derivatives for management of TMV and concludes through highlighting the future prospects via hoping that future pesticides will be safer for human being and our planet.